Application of model-informed drug development (MIDD) for dose selection in regulatory submissions for drug approval in Japan

Model-informed drug development (MIDD) is an approach to improve the efficiency of drug development. To promote awareness and application of MIDD in Japan, the Data Science Expert Committee of the Drug Evaluation Committee in the Japan Pharmaceutical Manufacturers Association established a task force, which surveyed MIDD applications for approved products in Japan. This study aimed to reveal the trends and challenges in the use of MIDD by analyzing the survey results. A total of 322 cases approved in Japan between January 2020 and March 2022 as medical products were included in the survey. Modeling analysis was performed in approximately half of the cases (47.8% [154/322]) and formed a major basis for the selection or justification of dosage and administration in approximately one-fourth of the cases [24.2% (78/322)]. Modeling analysis/model-based dose selection was frequently conducted in cases involving monoclonal antibodies, first indication, orphan drugs, and multi-regional trials. Moreover, the survey results indicated that modeling analyses contributed to dose optimization throughout the developmental phases, including changing dose levels from phase II to phase III and dose adjustment in special populations. Japanese data were included in most cases in which modeling analysis was used for dosage selection. Thus, modelling analysis may also address ethnic factors introduced in the ICH E5 and/or E17 guidelines. In summary, this survey is useful for understanding the current status of MIDD use in Japan and for future drug development.